Pairing Nanoparticles Geometry with TLR Agonists to Modulate Immune Responses for Vaccine Development.
Preeti Ravindra BhogeSandhya MardhekarSuraj ToraskarBalamurugan SubramaniRagahvendra KikkeriPublished in: ACS applied bio materials (2022)
Nanotechnology-based vaccine development necessitates understanding the crucial biophysical properties of nanostructures that alter immune responses. In this study, we demonstrate the synergistic effect of gold nanoparticles (AuNPs) shapes with toll-like receptor (TLR) agonists in immune modulation activity. Our results showed that CpG- and imidazoquinoline-conjugated rod-shaped AuNPs display relatively fast uptake by bone marrow-derived macrophage cells but exhibit poor immunogenic responses compared to their spherical and star-shaped AuNP counterparts. Surprisingly, star-shaped AuNPs exhibited intense pro-inflammatory cytokine secretion. Further mechanistic studies showed that star-shaped AuNPs were abundantly localized in the late endosome and lysosomal regions, whereas rod-shaped AuNPs were majorly sequestered in the mitochondrial region. These findings reveal that the shape of the nanostructures plays a pivotal role in driving the adjuvant molecules toward their receptors and altering immune responses.
Keyphrases
- toll like receptor
- immune response
- nuclear factor
- inflammatory response
- gold nanoparticles
- dendritic cells
- induced apoptosis
- early stage
- oxidative stress
- gene expression
- dna methylation
- photodynamic therapy
- signaling pathway
- single cell
- cell cycle arrest
- endoplasmic reticulum stress
- cancer therapy
- case control
- pi k akt